A therapeutic antibody targeting annexin-A1 inhibits cancer cell growth in vitro and in vivo.

Autor: Al-Ali HN; Anglia Ruskin University, School of Life Science, Faculty of Science and Engineering, East Road, Cambridge, CB1 1PT, UK., Crichton SJ; Medannex Ltd, 1 Lochrin Square, 92-98 Fountainbridge, Edinburgh, Scotland, EH3 9QA, UK., Fabian C; Medannex Ltd, 1 Lochrin Square, 92-98 Fountainbridge, Edinburgh, Scotland, EH3 9QA, UK., Pepper C; Brighton and Sussex Medical School, Medical Research Building, Falmer, Brighton, BN1 9PX, UK., Butcher DR; Anglia Ruskin University, School of Life Science, Faculty of Science and Engineering, East Road, Cambridge, CB1 1PT, UK., Dempsey FC; Medannex Ltd, 1 Lochrin Square, 92-98 Fountainbridge, Edinburgh, Scotland, EH3 9QA, UK., Parris CN; Anglia Ruskin University, School of Life Science, Faculty of Science and Engineering, East Road, Cambridge, CB1 1PT, UK. Chris.parris@aru.ac.uk.
Jazyk: angličtina
Zdroj: Oncogene [Oncogene] 2024 Feb; Vol. 43 (8), pp. 608-614. Date of Electronic Publication: 2024 Jan 10.
DOI: 10.1038/s41388-023-02919-9
Abstrakt: In this study we conducted the first investigation to assess the efficacy of a novel therapeutic antibody developed to target annexin-A1 (ANXA1). ANXA1 is an immunomodulatory protein which has been shown to be overexpressed in, and promote the development and progression of, several cancer types. In particular, high ANXA1 expression levels correlate with poorer overall survival in pancreatic and triple-negative breast cancers, two cancers with considerable unmet clinical need. MDX-124 is a humanised IgG1 monoclonal antibody which specifically binds to ANXA1 disrupting its interaction with formyl peptide receptors 1 and 2 (FPR1/2). Here we show that MDX-124 significantly reduced proliferation (p < 0.013) in a dose-dependent manner across a panel of human cancer cell lines expressing ANXA1. The anti-proliferative effect of MDX-124 is instigated by arresting cell cycle progression with cancer cells accumulating in the G 1 phase of the cell cycle. Furthermore, MDX-124 significantly inhibited tumour growth in both the 4T1-luc triple-negative breast and Pan02 pancreatic cancer syngeneic mouse models (p < 0.0001). These findings suggest ANXA1-targeted therapy is a viable and innovative approach to treat tumours which overexpress ANXA1.
(© 2024. The Author(s).)
Databáze: MEDLINE
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